I We wish to continue our study of genes needed for neuronal differentiation and function in th nematode Caenorhabditis elegans. Most of the research will center, as in the past, on the analysis o the development and activity of a set of six touch receptor neurons (the touch cells). Previous researc under this grant has led to the identification of over 500 mutations that render the animal touc nsensitive. These mutations define 17 genes needed for the generation, specification, maintenance, and function of the touch cells. Four of these genes and eight others that do not mutate to touch nsensitivity act combinatorially in the development of the cells, allowing them to express cell-specific eatures and restricting their number to six. The remaining genes encode products that are needed for he function of the cells. We have developed a model in which the proteins encoded by twelve of thesi genes are components or modulators of the mechanosensory apparatus needed by the cells to sens' ouch. This isthe first molecular model for a eukaryoticmechanicalsense. Inthe upcoming grant period) /e wish to investigate how this combinatorial control specifies touch cell fate, uncover new touch-cell pecific genes, and test predictions of our model of mechanosensation. The specific aims of th proposal are: 1) to characterize combinatorial regulation of touch cell fate. 2) To identify and characterize new genes needed for touch cell development and function. 3) To continue the molecular genetic characterization of genes whose products are needed for mechanosensation. To investigate the electrophysiological properties of a) wild-type and mutant touch cells in situ and b) touch-cell function proteins in Xenopus oocytes.